Project Summary The 90+ Study was initiated January 1, 2003 as a population-based sample of oldest-old survivors of the Leisure World Cohort Study (LWCS, enrollment 1981-1984). With more than 1,800 participants, The 90+ Study is one of the largest and longest studies in the world of dementia, cognitive decline, disability, and frailty in the oldest-old. People over 90 are the fastest segment of the population and have the greatest public health impact as the risk of dementia is extraordinarily high in these individuals, reaching a staggering 40% per year in centenarians. However, many oldest old maintain superior cognitive performance well into their tenth decade and beyond (cognitive resilience), often in the presence of neuropathological changes (cognitive resilience in the presence of pathology). Lifestyle, co-morbid conditions, genetics, and other factors have been implicated in this cognitive resilience, but have not been well studied. In this application, we extend our studies to investigate cognitive resilience in these remarkable individuals. In Aim 1, we consider early (30 years earlier in the LWCS) and late (at age 90+) lifestyle and other factors in relation to cognitive resilience. Factors related to the maintenance of superior cognitive abilities in the presence of pathology are investigated in Aim 2. Taking advantage of our large cohort of 90+ year-olds in our imaging studies, we prospectively follow individuals without dementia to estimate incidence of dementia and rates of cognitive decline in relation to MRI and PET biomarkers in Aim 3. We analyze the role of low levels of multiple neuropathologic changes in the expression of dementia in Aim 4. Finally, with this application, we will recruit the last living LWCS participants eligible for our study, and complete ascertainment of all previously established outcomes in The 90+ Study (dementia, CIND, MCI, frailty, disability, and mortality). We will make this dataset spanning almost four decades publically available to the research community (Aim5). With our extensive database, unique large cohort of well-characterized individuals, extensive and multidisciplinary longitudinal follow-up, and innovative neuropathological and neuroimaging investigations, we are ideally positioned to do studies of dementia and resilience in the oldest-old. Identifying factors related to cognitive resilience and dementia, including modifiable lifestyle factors and imaging biomarkers, would contribute to our understanding of aging in health and disease and provide potential targets for interventions to promote successful aging.